Glycogen Synthase Kinase 3 (GSK3)
 Ligand in GSK3 active site
Ligand in GSK3 active site.
Docking example from OTAVAchemicals GSK3 focused library.
The detection of H-bonding between ligand and key GSK3 residue (Val135) was used for the library preparation.

Glycogen synthase kinase-3 (GSK3) was initially identified more than two decades ago as an enzyme involved in the control of glycogen metabolism. In recent years it has been shown to have key roles in regulating a diverse range of cellular functions, which have prompted efforts to develop GSK3 inhibitors as therapeutics.

GSK3 inhibitors have now been shown to be effective in normalizing blood glucose levels in animal models of type 2 diabetes, with their effects seeming to occur primarily through an increase in hepatic glycogen synthesis and a decrease in hepatic gluconeogenesis.

GSK3 inhibitors might also have potential for neurodegenerative disorders, such as Alzheimer's disease. For example, there is recent evidence that GSK3 increases the production of β-amyloid — which has a key role in the pathogenesis of Alzheimer's disease — and that inhibition of GSK3 might reduce β-amyloid levels.

The focused libraries, including docking scores and drug-like properties, are available on request.

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Philip Cohen & Michel Goedert. GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov. 2004 Jun;3(6):479-87.